Synthesis and characterisation of supramolecular gels with amide and urea
functionality.
Daníel Arnar Tómasson
Efnafræðideild
Háskóli Íslands
2017
i
Synthesis and characterisation of supramolecular gels with amide and urea
functionality. Smíði og greining á þversameinda gelum með amíð og
þvagefna virkni.
Daníel Arnar Tómasson
15 eininga ritgerð sem er hluti af
Baccalaureus Scientiarum gráðu í lífrænni og ólífrænni efnafræði
Leiðbeinandi
Krishna Kumar Damodaran
Efnafræðideild
Verkfræði- og náttúruvísindasvið Háskóli Íslands
Reykjavík, Mars 2017
ii
Synthesis and characterisation of supramolecular gels with amide
and urea functionality. Smíði og greining á þversameinda gelum
með amíð og þvagefna virkni
15 eininga ritgerð sem er hluti af Baccalaureus Scientiarum gráðu í
efnafræði
Höfundarréttur © 2017 Daníel Arnar Tómasson
Öll réttindi áskilin
Efnafræðideild
Verkfræði- og náttúruvísindasvið
Háskóli Íslands
Hjarðarhaga 2-6
107 Reykjavík
Sími: 525 4000
Skráningarupplýsingar:
Daníel Arnar Tómasson, 2017, Synthesis and characterisation of
supramolecular gels with amide and urea functionality, BS ritgerð,
efnafræðideild, Háskóli Íslands, 55 bls.
ISBN XX
Prentun:
Reykjavík, 10.apríl 2017
iii
Declaration of Authorship
I, Daníel Arnar Tómasson, declare that this thesis titled, Synthesis and
characterisation of supramolecular gels with amide and urea
functionality’ and the work presented in it are my own.
I confirm that:
This work was done wholly or mainly while in candidature for a research
degree at this University.
Where any part of this thesis has previously been submitted for a degree
or any other qualification at this University or any other institution, this
has been clearly stated.
Where I have consulted the published work of others, this is always
clearly attributed.
Where I have quoted from the work of others, the source is always given.
With the exception of such quotations, this thesis is entirely my own
work.
I have acknowledged all main sources of help.
Where the thesis is based on work done by myself jointly with others, I
have made clear exactly what was done by others and what I have
contributed myself.
Signed:________________________________________________
Date:__________________________________________________
iv
Útdráttur
Vinsældir rannsókna á þversameindagelum hafa aukist gríðarlega síðta áratuginn. Þessar
auknu vinsældir má rekja til þeirra ótal möguleika sem sem þetta svið bíður upp á, eins og
dínamísk gel, lífræðilegar rannsóknir þar sem gelin eru notuð til frumu ræktunar og sem
miðill til þess að stjórna kristalvexti. Auk þess sem auknar rannsóknir á
þversameindagelum gætu hjálpað að auka skilning á efnafræði ósamgildra tengja.
Þversameindagel myndast via ósamgild tengi, eins og vetnistengi, van der Waals krafta
π−π stacking etc, þar sem uppleystar sameindir raða sér saman í einskonar súlur eða keðjur
sem svo mynda svokallaða fibrala. Fibralarnir mynda svo þrívíðan óreggluglegan strúktúr
sem festir leysinn og myndast við það gel. Bygging og eiginleikar þversamaneinda gelanna
eru að mestu niðurkomin á byggingareiningum, staðsetningum hópa sem mynda ósamgild
tengi í sameindinni og eiginleikum ósamgildu tengjanna. Vetnis tengi hafa reynst vera
mikilvægur hluti af þversameinda gelum og varð bis-urea motif því fyrir valinu sem
grunnur samaeinda fyrir þetta verkefni. Bis-urea motif eru þekkt fyrir að mynda α-tape,
fibril kerfið myndar svo þrívítt kerfi sem festir leysinn og myndar gel. Tilgangur þessa
verkefnis var að hanna, smíða og prófa ný efni sem höfðu möguleika á að reynast vel sem
þversameindagel. Auk þess að gera prófanir á þekktu þversameindageli. Öll efnin voru
prófuð til gelmyndunar í mismunandi leysum og styrk.
Abstract
Supramolecular gels based on low molecular weight gelators (LMWGs) have witnessed a
tremendous growth over last decade due to the emerging potential applications such as
dynamic gels, biological applications using gels as cell growth media and also medium to
control crystal growth, drug delivery etc. LMWGs are formed by the immobilisation of the
solvent molecules in the 3-D network of the gelators via non-covalent interactions such as
hydrogen bonding, van der Waals interactions, π−π stacking etc. The structure and
properties of the supramolecular gels rely mostly on the geometry of the building blocks
and spatial arrangement and nature of the intermolecular non-covalent interactions. The
hydrogen bonding motif in gelator plays a crucial role in gel formation. In this BS project,
urea motif have been chosen as hydrogen bonding motif since bis-urea motif is well known
to form α-tapes, which gel to give a fibre surface. The urea groups in the molecule form
strong non-covalent bonds (hydrogen bonds) creating long chains of molecules, which
form fibrils that then form the 3D network of the gel. In this context, a series of bis-urea
compounds based on amino acids were designed, synthesised and characterised by
standard analytical methods. Gelation ability in various solvent and the gel strength have
been analysed for all amino acid based compounds synthesised in this BS-project.
v
Contents
Declaration of Authorship ................................................................................................ iii
Abstract ............................................................................................................................... iv
Contents ............................................................................................................................... v
List of Figures ..................................................................................................................... x
Tables .................................................................................................................................. ix
Abbreviations ...................................................................................................................... x
Acknowledgements ............................................................................................................ xi
1 Introduction .................................................................................................................. 1
1.1 Understanding supramolecular architecture ................................................................ 2
1.2 Urea based supramolecular gels ................................................................................. 4
1.3 Amino acid based gelators .......................................................................................... 5
2 Amis and Objectives ...................................................................................................... 6
2.1 Enantiomers, racemic mixtures and conglomerates ................................................... 8
3 Experimental Section ................................................................................................... 9
3.1 Materials and methods ..................................................................................................... 9
3.2 Synthesis .......................................................................................................................... 9
3.2.1 General synthesis of amino acid methyl ester hydrochloride .................................. 9
3.2.2 General synthesis of amino acid-methyl-ester-hydrochloride-bis-urea-hexyl ....... 10
3.3 Solubility/gelation and gel straight tests ........................................................................ 12
3.3.1 Solubility test ......................................................................................................... 12
3.3.2 Gelation test at higher concentration ..................................................................... 12
3.3.3 Tgel test ................................................................................................................... 12
vi
4 Results and Discussion ................................................................................................ 13
4.1 Synthesis ......................................................................................................................... 13
4.1.1 Synthesis of amino acid esters ................................................................................ 13
4.1.2 Synthesis of gelators. .............................................................................................. 14
4.2 Gelation tests .................................................................................................................. 14
4.2.1: 1 wt% solvent test .................................................................................................. 15
4.2.2 Gel tests at a higher concentration .......................................................................... 17
4.3 Tgel test. ........................................................................................................................... 18
5 Conclusion .................................................................................................................... 22
6 Supplementary Information ........................................................................................ 26
6.1 Solvent table ................................................................................................................... 26
6.2 Nuclear Magnetic Resonance Spectroscopy .................................................................. 26
6.2.a General .................................................................................................................... 26
6.2.x Spectral data ........................................................................................................... 26
6.2.1: 1H-NMR of D-L-phenylalanine-methylester 26
6.2.2: 1H-NMR of L-phenylalanine-methylester 27
6.2.3: 1H-NMR of D-L-phenylglycine-methylester 27
6.2.4: 1H-NMR of L-valine-methylester-bisurea-hexyl 28
6.2.5: 1H-NMR of L-valine-methylester-bisurea-hexyl-b 28
6.2.6: 1H-NMR of D-valine-methylester-bisurea-hexyl 29
6.2.7: 1H-NMR of D-L-valine-methylester-bisurea-hexyl
29
6.2.8: 1H-NMR of L-phenylglycine-methylester-bisurea-hexyl 30
6.2.9: 1H-NMR of D-phenylglycine-methylester-bisurea-hexyl 30
6.2.10: 1H-NMR of D-L-phenylglycine-methylester-bisurea-hexyl 31
6.2.11: 1H-NMR of L-phenylalanine-methylester-bisurea-hexyl 31
6.2.12: 1H-NMR of D-phenylalanine-methylester-bisurea-hexyl 32
6.2.13: 1H-NMR of D-L-phenylalanine-methylester-bisurea-hexyl 32
vii
List of Figures
1.1: Scheme describing the formation of supramolecular gels 1
1.2: The generic a) primary, b) secondary and c) tertiary structures
of a urea based supramolecular gel 2
1.3: SEM images of Phenylalanine-methylester-bisurea- hexyl 3
1.4: Stacking of urea groups 4
2.1: Molecular structure of all gelators synthesized for this project 7
4.1: Mechanism of esterification using thionyl chloride 13
4.2: Mechanism of synthesis for gelator molecules 14
4.3: Gels of 3L in toluene and ethyl acetate 16
4.4: Gels of 2D in o-xylene, nitrobenzene and ethanol 18
6.1: 1H-NMR of D-L-phenylalanine-methylester 26
6.2: 1H-NMR of L-phenylalanine-methylester 27
6.3: 1H-NMR of D-L-phenylglycine-methylester 27
6.4: 1H-NMR of L-valine-methylester-bisurea-hexyl 28
6.5: 1H-NMR of L-valine-methylester-bisurea-hexyl-b 28
6.6: 1H-NMR of D-valine-methylester-bisurea-hexyl 29
6.7: 1H-NMR of D-L-valine-methylester-bisurea-hexyl 29
6.8: 1H-NMR of L-phenylglycine-methylester-bisurea-hexyl 30
6.9: 1H-NMR of D-phenylglycine-methylester-bisurea-hexyl 30
6.10: 1H-NMR of D-L-phenylglycine-methylester-bisurea-hexyl 31
6.11: 1H-NMR of L-phenylalanine-methylester-bisurea-hexyl 31
6.12: 1H-NMR of D-phenylalanine-methylester-bisurea-hexyl 32
6.13: 1H-NMR of D-L-phenylalanine-methylester-bisurea-hexyl 32
6.14: Mass of L-valine-methylester-bisurea-hexyl 33
6.15: Mass of D-valine-methylester-bisurea-hexyl 33
viii
6.16: Mass of D-L-valine-methylester-bisurea-hexyl 34
6.17: Mass of L-phenylglycine-methylester-bisurea-hexyl 34
6.18: Mass of D-phenylglycine-methylester-bisurea-hexyl 34
6.19: Mass of D-L-phenylglycine-methylester-bisurea-hexyl 35
6.20: Mass of L-phenylalanine-methylester-bisurea-hexyl 36
6.21: Mass of D-phenylalanine-methylester-bisurea-hexyl 36
6.22: Mass of D-L-phenylalanine-methylester-bisurea-hexyl 37
ix
Tables
4.1: Solvent tests for amino acid based urea gelators, at 1 wt%/V 15
4.2: Gel test for all enantiomers of 1 in different solvents. 17
4.3: Gel test for all enantiomers of 2 in different solvents 18
4.4: Tgel test for all enantiomers of 2 that gelled 19
4.5: Tgel test for all enantiomers as well as conglomerate mixture
(50/50 by weight) of D and L for 3 in ethyl acetate and toluene 20
6.1: Numbering scheme for solvents 25
x
Abbreviations
LMWG Low molecular weight gelator
LMOG Low molecular organo gelator
SAFIN Self –assembled fibiral network
RB Round bottom boiling flask/ round bottom
Wt% Weight percentage
Tgel Temperature at which gel becomes solution (gel-sol temperature)
1-D One dimensional
3-D Three dimensional
xi
Acknowledgements
I would like to give my thanks to my lab mates and friends at Science
Institute
Special thanks go to my co-workers in the lab, especially Dipankar Ghosh as
well as my supervisor, Krishna, for advice and help in this project.
I would also like to thank Dr. Sigríður Jónsdóttir for carrying out
spectroscopic measurements.
But most of all I want to thank my mother for listening to me talk about my
project for hours on end, even though she only has rudimentary understanding
of chemistry and usually never understood what I was going on about.
1
1 Introduction
Gels are a fascinating thing, instantly recognised, a form of matter intermediate, which is
an between solid and liquid, and can be found in most places from the home to the
laboratory. They range from beauty products such as hair gels and shaving creams, gels
used for cooking such as gelatine, to lithium grease, contact lenses, gels used for cultivate
bacteria in laboratories and as crystal growth media and so on. Gels are composed of two
factors, the gelating solid-(a gelator)-, and a solvent. When combined a solid like material
is formed, a stiff, somewhat flexible, soft solid. The gelator traps or immobilizes the
solvent in a network of fibrils (either long cross linked chains or polymeric chains), which
cross link to form a tangled network throughout the solution trapping the solvent in place.
For most common and commercially available gelators the network is a three dimensional
one (3-D), formed when the gelator molecules form polymers, such gels are called
polymeric gels. However if the 3-D network is formed by a self-assembly process, that is
with non-covalent interactions like van der Waals interactions, π-π stacking, hydrogen
bonding etc. the resulting gel is called a supramolecular gel. In that case the 3-D network is
made up of 1-D fibrils, which are crosslinked to form the 3D network (See figure 1.1).1-3
Such type of supramolecular gels will be the focus of this thesis.
Figure 1.1 : Scheme describing the formation of supramolecular gels.
Low molecular weight gelators (LMWGs) are a large class of gelating materials, usually
<3000 amu/molecule strictly belong to the category of supramolecular gelators.
Supramolecular gels1,3,4 can be classified either as organogels or hydrogels depending on
the solvent medium being either an organic solvent or water. However compounds that
form organogels generally don’t form hydrogels and vice versa.2 These types of gelators
2
(both organogels and hydrogels) have gained a tremendous growth in popularity over last
decade due to the emerging potential applications of such as dynamic gels, biological
applications using gels as cell growth media and also medium to control crystal growth,
drug delivery etc. Furthermore, the diverse nature of LMWGs means that most of the
solvents can be gelled, due to the wide range of chemical species that form gels, including
amino acids, bis-ureas, sugars, surfactants, fatty acids and others.5 The multitude of
different solvents and diverse chemical species that can form supramolecular gels clearly
indicate the advantages over traditional gels.
One of main advantages is the reversibility of gelation process using a variety of
methods. The transformation (gel-sol) can be triggered by changes in temperature, pH,
sonication, and irradiation or even by addition of a chemical trigger in the form of
anions.1,3,6,7 The sensitivity of gels to one (or all respectively) of these gel-sol triggers can
also be used as a measure of the strength of the gel. Generally, supramolecular gels are
formed by heating a solution of particular compounds in in an appropriate solvent,
typically 1 wt % (1.0 mg in 1 mL) to form a solution and when cooled to room
temperature. When the temperature drops below the sol-gel transition temperature (Tgel)
they form gels, which will be able trap the solvent and upon inversion they hold the liquid.
1.1 Understanding supramolecular architecture.
As stated earlier supramolecular gels, sometimes called physical gels, are made out of a 3-
D network of 1-D fibrils, in which the solvent is immobilized. The fibrils are formed via
non-covalent interactions between gelator molecules.
Figure 1.2: The generic a) primary, b) secondary and c) tertiary structures of a urea based supramolecular gel8
3
The primary structure of a gel is generated when the individual gelator molecules self-
assemble via non-bonding interactions to form a one dimensional tape like network (fibrils).
These fibrils aggregate to form various secondary structures such as fibres, sheets, micelles,
ribbons and helices. However, fibres and ribbons are most observed in supramolecular gels
based on urea (Figure 1.2).8 The self-assembled fibiral networks (SAFINs) revile various
morphological features when looked at microscopically, using optical microscopy,
scanning electron microscopy, transition electron microscopy or even atomic force
microscopy. Most noteworthy of SAFINs is the high ratio of branching and or
entanglement of the fibrils (responsible for the gels solvent trapping 3D network).1
Topologically, the fibril network can be broken down into a system of nodes (junctions,
either transient or permanent, providing rigidity to the microstructure of the gel) and edges
(fibrils, which form connection between junctions).9
Figure 1.3: SEM images of (A) D, (B) L and (C) D-L Phenylalanine-methylester-bisurea-hexyl gels in ethyl
acetate displaying fibrous network
The understanding of the structure of supramolecular gels in gel state is still in its
infancy because of the low ordering of the gels and predicting the interactions mentioned
above to see if a compound is potentially able to form gels is difficult. It has been shown
that formation of 1-D hydrogen bonded fibrils favours gel formation1,10. X-ray
crystallography data can help us see if a compound is capable of making 1-D fibrils. By
analysing the crystal structure of a compound, we can see if hydrogen bonds (the strongest
of non-covalent interactions) are propagated along only one of the molecules axes, that is
either along x,y or z-axis. The single crystal structure of gelator can be correlated to that of
the gel state by comparing with the structures of xerogels (dried gel).10 This falls under the
field of crystal engineering and is a very important factor of LMOG designing and the key
structural features of gel-network formation in LMWGs can be identified using
4
Figure 1.4: Stacking of urea
groups
supramolecular synthons.1 In this BS project, urea motif have been chosen as
supramolecular synthons that can form α-tapes, which will give a fibre surface.7
1.2 Urea based supramolecular gels
The focus of this thesis will be on urea based gelators. In 1990s, van Esch et al. analysed
the aggregation of the fibres into an extended 3-D network in certain solvents and found
that the fibres form extended 1-D networks via hydrogen
bonding with highly directional strands and further
aggregation of these strands will form 3-D networks that could
trap the solvents in these networks.11 A wide range of urea
based gelators have been synthesised and characterised with
excellent potential applications.12 More explicitly gelators
containing a hydrocarbon chain linked to an amino acid trough
with a urea group. But why is the urea group important?
The most important building block of supramolecular
gels is the hydrogen bond (a non-covalent bond formed
between a hydrogen atom and either a nitrogen, oxygen or
fluorine atom) the strongest of non-covalent bonds. Because of
the special arrangement of amides and the ketone groups in the
urea all bonds lie in one axis. This is because of the sp2 arrangement of bonding orbitals,
both nitrogen atoms as well as the carbon, arranging all bonding orbitals in this part of the
molecule in triangular planar symmetry. (See figure 1.4). This in term causes the bonds to
form in a 1-D fashion, providing self-assembly via hydrogen bonding.1 The stacked
molecules then form an α-tape motif, the fibril, which then form the 3D network. Solvent
molecules are sometimes trapped in the helical chain distorting the urea tape. It is this
strong directionality of the hydrogen bonds and the chains (α-tapes) formed that leads to
the formation of the fibres in high concentration and the formation of the gel.4, 5 The
functional groups chosen in addition to urea moiety was amino acid due to their biological
importance, availability and cost efficient source of amines.
5
1.3 Design of Amino acid based gelators
Bis- and tris(urea) LMWGs, particularly bearing long alkyl substituents, have proved to be
highly effective gelators, on top of that it has been shown that chiral LMWGs form helical
fibrous structures. Amino acid based gelators fall into both categories and have proven to
be quite successful.13-15 All amino-acids are chiral, and show some diversity in structure,
though they all have the same back bone. They are neither very polar nor non polar. In
designing a potential gelator containing an amino acid/s one gets the potential for great
diversity of gelators. In the design of the reaction used here the amino acids give one of the
nitrogen atoms that form the urea (from the amide group in the backbone of every amino
acid). This makes it possible to use a relatively simple type of reaction to make a diverse
group of amino acid based gelators/potential gelators. Amino acids are easily accessible
and relatively cheap making them an even more practical base for LMWGs. On top of that
they are all chiral, meaning that they have D and L isomers. Furthermore, a range of
functionalities can be introduced by altering the substituent groups (R) of the amino
acids.16
In this project, a series of bis-urea compounds based on amino acids were designed,
synthesised and characterised by standard analytical methods. Gelation ability in various
solvent and the gel strength have been analysed for all amino acid based compounds
synthesised in this BS-project. The properties of the gel such as Tgel, gel-sol/sol-gel etc are
largely due to gel-solvent interaction and different solvents often give a slightly different
gel (with the same gelator).1,4,8 Differences in for example gel-sol temperature and
appearance of the gel, like colour and/or transparency of the gel, can often be observed,
evidence of this will be presented in later chapters.
6
2. Aims and objectives
The aim of this project is to develop supramolecular gels based on amino acid and urea
modify and to evaluate the gelation properties. The main aims are
• To design new potential LMWGs based on bis-urea motif and amino acids.
• To synthesize and characterize these compounds and compare with reported amino acid
gels.
• Test the gelation properties of these compounds and find the appropriate solvent and
concentration for gel formation.
• Compare the gelation properties with the reported amino acid gels.
• Determine gel strength and compare with enantiomers, racemic and conglomerate
mixtures.
As mentioned above the interest in supramolecular gels/gelators has spiked in the last
decades. This is because of the possibilities it provides as for example a medium to control
crystal growth, as a drug delivery system and many more. For this reason designing and
creating new gelators is both interesting and important. Dr. Damodaran’s group has already
found phenylalaninemethylester bis-urea compounds are excellent gelators, two new -
amino acid based urea compounds were designed (Figure 2.1). Furthermore, it is important
to evaluate the strength of these supramolecular molecular networks in these gels. A
detailed description of both a gelation/solubility test and the Tgel test can be found in the
experimental section. Thus, a series of amino acids based urea compounds will be
synthesised following the reactions procedure for 3, and determine if compounds 1 and 2
would gel. One of the interesting factors of having amino acids in that they could provide a
well resolved source of chirality or we could synthesise a series of compounds from the
same amino acids such as enantiomers, racemic mixtures and conglomerates.
7
_________________________________________________________________________
Figure 2.1: Molecular structure of all both new potential gelators, Valine-methylester-bisurea-hexyl, 1, and
phenylglycine-methylester-bisurea-hexyl, 2, as well as already established gelator phenylalanine-methylester-
bisurea-hexyl, 3.
8
2.1 Enantiomers, racemic mixtures and conglomerates
Since all amino acids are chiral and the derivatives of amino acids should be chiral. Chiral
compounds exist as enantiomers, usually represented as D and L (where D or L is
determined by the direction the compound turns light) or S and R (determined by the
orientation (clockwise or counter clockwise/left or right spin) of the highest to second
lowest ordered groups in the chirality centre). Structually enantiomers are exactly the same
except they are mirror images of each other, and NON-superimposable. A good example of
a chiral object are human (and other primate) hands, which are exactly the same but no
matter how you twist or turn them you can never arrange them in a way so they have the
same orientation and do not overlap (that is you cannot superimpose them). In nature as
well as in in-vitro reactions, chiral molecules (D and L isomers) are produced at
(relatively) the same rate, resulting in a racemic mixture (a mix of 50% D and L). The
enantiomers can then be separated to create either D or L specific compounds.
Interestingly, we could modify synthetic conditions in lab and produce one stereoisomer
over another stereoisomer, which is known as asymmetric synthesis. Since, the isomers
(enantiomers) or the racemic mixture are commercially available it possible to modify the
same molecule but with different chirality, mixed chirality (different enantiomers) or
conglomerate mixture. A conglomerate is defined by the Oxford dictionary as: “A thing
consisting of a number of different and distinct parts or items that are grouped together”. In
this project, conglomerate mixture will be prepared by mixing 50/50 mix (by weight) of D
and L enantiomers together. Theoretically there should be no difference in between the
enantiomers and the two mixed systems except the direction they turn light but will the
chirality effect the gelation or strength of the gel? Thus, it will be interesting to see the
variation in gelation/gel strength between racemic and conglomerate mixture. A solvent
test will be carried out for each compound and conglomerate mixture at 1 wt% in various
solvents to determine solubility and gelation potentials. If the solution did not gel but
showed some characteristics of a possible gelator (for example a slightly cloudy or
coagulant solution) the wt% was raised for that solvent and an additional gel test
preformed.
9
3 Experimental
3.1 Materials and methods
All starting materials were purchased from commercial sources and were used as supplied.
The chloroform was purified with simple distillation with P2O5 to remove water from the
solvent. The solution was refluxed for 3 hours and then distilled. Methanol used was new
and very pure <99% and was freshly distilled from Mg turnings. The method used was
Lund and Bjerrum reaction with magnesium ethoxide. 5g of clean dry magnesium turnings
and 0.5g of iodine where added to a 2L RB with around 50-100 mL of MeOH, iodine was
added to activate the Mg, the mixture was warmed until a vigorous reaction occurs. When
this subsides, heating is continued until all the magnesium is converted to magnesium
ethoxide. 1L of ethanol was then added (no more can be added), after an hour's reflux it
was distilled off. The water content should be below 0.05%. All water used was deionised.
1H NMR spectrums were recorded on a Bruker Advance 400 spectrometer.
3.2 Synthesis
3.2.1 General synthesis of amino acid methyl ester hydrochloride
The reaction was conducted under nitrogen. In a typical experiment, 10 mL of thionyl
chloride (SOCl2) was added dropwise to 60 mL of anhydrous methanol, MeOH, in a 250
mL RB, at approximately 0°C (cooled in ice bath). A suspension of the amino acid (30
mmol, in these cases phenylalanine and phenylglycine) in anhydrous MeOH was then
added to the solution and a minimal amount of MeOH was then used to make sure all
amino acid is transferred to the solution. The RB was then removed from the ice bath and
the solution was equilibrated to room temperature before being refluxed at 70°C for 18
hours or overnight. The solvent was then removed under reduced pressure producing a
white precipitate/residue [note that SOCl2 is a volatile chemical and can cause harm to both
you and the rotavapor so an alternative way of removing solvent (and SOCl2) could be
used for example to distilling the solvent under vacuum or nitrogen]. The
precipitate/residue was re-dissolved in MeOH and that solution was added drop wise into
250 mL of ether. A fine white precipitate was formed which was filtered and washed with
10
additional ether and then left to dry in a fumehood. The typical yield for this reaction is
between 80-90 %.
This procedure was used to synthesise D-L-phenylalanine (A1), L-phenylalanine (A2) and
D-L-phenylglycine (A3)
A1 1H NMR (400 MHz, Chloroform-d) δ 8.81 (s, 2H), 7.30 (q, J = 4.4 Hz, 5H), 4.46 (t, J =
6.5 Hz, 1H), 3.71 (s, 3H), 3.53 – 3.35 (m, 2H).
A2 1H NMR (400 MHz, DMSO-d6) δ 8.76 (s, 3H), 7.39 – 7.14 (m, 5H), 4.27 – 4.15 (m,
1H), 3.66 (s, 3H), 3.26 – 2.99 (m, 2H).
A3 1H NMR (400 MHz, DMSO-d6) δ 7.23 (d, J = 47.7 Hz, 5H), 6.10 (s, 2H), 4.40 (t, J =
8.0, 5.6 Hz, 1H), 3.59 (s, 3H).
See chapter 6, Supplementary information, for NMR spectra.
3.2.2 General synthesis of amino acid-methyl-ester-hydrochloride-bis-
urea-hexyl
The amino acid (11,93 mmol) is dissolved in 100 mL of freshly distilled chloroform in a
250 mL two necked RB and around 3 mL of triethylamine added slowly (exact volume is
not important since this is just added to help dissolve the amino acid, add until solution is
mostly clear, note that triethylamine evaporates slowly and is not easy to get out with
rotavapor so do not add in excess). A dropping funnel was then placed on the RB and the
system put under nitrogen. A solution of 1,6 diisocyanatohexane (5,97 mmol, 1,0 g,
0,95mL) in chloroform (50 mL) was added to the dropping funnel under nitrogen and was
added to the drop wise to the solution under stirring over a period of an hour. After
addition the dropping funnel was replaced with a glass stopper. The solution was then
refluxed for 16 hours/overnight and was cooled to room temperature. The solvent was
removed under reduced pressure leaving a white slurry and the RB flask was left in a
fumehood until all triethylamine has evaporated (approximately 1-3 days depending upon
how much is used/ size of the batch). After all triethylamine has evaporated and the slurry
become a solid, it is washed with water. This was done by adding water to the RB and
stirred for 4 hours or longer. The solid was then filtered out, washed with additional water
11
and then dried. The typical yield for this reaction was between 70-80 %. See chapter 6,
Supplementary information, for NMR spectra.
Valine-methylester-bisurea-hexyl
1L: 1H NMR (400 MHz, DMSO-d6) δ 6.41 (d, J = 8.8 Hz, 1H), 6.13 (d, J = 8.8 Hz, 1H), 5.99 (s,
1H), 5.73 (s, 1H), 4.09 – 4.04 (m, 2H), 3.63 (s, 6H), 2.96 (s, 5H), 2.03 – 1.93 (m, 2H), 1.38 – 1.22
(m, 10H), 0.85 (d, J = 8.9 Hz, 12H). HRMS (APCI) Calcd for C20H38N4O6 430.28; found 453.2668
[M+Na]+
1Lb: 1H NMR (400 MHz, Chloroform-d) δ 5.49 (s, 2H), 5.17 (s, 2H), 4.36 (s, 2H), 3.66 (s, 6H),
3.11 (d, J = 41.6 Hz, 5H), 2.05 (s, 2H), 1.39 (s, 4H), 1.26 (s, 4H), 0.92 – 0.78 (m, 12H).
1D : 1H NMR (400 MHz, DMSO-d6) δ 6.12 (d, J = 8.8 Hz, 2H), 5.99 (t, J = 5.6 Hz, 2H), 4.07 (dd, J
= 8.8, 5.5 Hz, 2H), 3.62 (s, 6H), 2.97 (d, J = 6.3 Hz, 4H), 1.97 (dd, J = 6.8, 1.4 Hz, 2H), 1.34 (d, J =
6.6 Hz, 4H), 1.25 (d, J = 3.8 Hz, 5H), 0.84 (dd, J = 10.0, 6.8 Hz, 12H). HRMS (APCI) Calcd for
C20H38N4O6 430.28; found 453.2684 [M+Na]+
1D-L: 1H NMR (400 MHz, DMSO-d6) δ 6.13 (s, 2H), 5.98 (t, J = 5.6 Hz, 2H), 4.07 (dd, J = 8.8, 5.5
Hz, 2H), 3.62 (s, 6H), 2.97 (s, 4H), 2.00 – 1.91 (m, 2H), 1.35 (s, 5H), 1.25 (s, 5H), 0.84 (d, J = 3.3
Hz, 12H). HRMS (APCI) Calcd for C20H38N4O6 430.28; found 453.2657 [M+Na]+
Phenylglycine-methylester-bisurea-hexyl
2L: 1H NMR (400 MHz, DMSO-d6) δ 7.35 (s, 10H), 6.69 (s, 2H), 3.62 (s, 6H), 2.98 (s, 4H), 1.29
(d, J = 45.4 Hz, 9H). HRMS (APCI) Calcd for C24H34N4O6 498.25; found 521.2371 [M+Na]+
2D: 1H NMR (400 MHz, DMSO-d6) δ 7.35 (s, 11H), 7.06 (d, J = 7.7 Hz, 1H), 6.70 (d, J = 7.8 Hz,
1H), 6.06 (s, 1H), 5.27 (d, J = 7.8 Hz, 2H), 3.62 (s, 6H), 2.98 (s, 4H), 1.29 (d, J = 45.9 Hz, 8H).
HRMS (APCI) Calcd for C24H34N4O6 498.25; found 521.2371 [M+Na]+
2D-L: 1H NMR (400 MHz, DMSO-d6) δ 7.36 (h, J = 7.9 Hz, 11H), 6.71 (d, J = 7.7 Hz, 2H), 6.07 (t,
J = 5.8 Hz, 2H), 5.28 (d, J = 7.6 Hz, 2H), 3.62 (s, 6H), 2.98 (p, J = 6.4 Hz, 5H), 1.35 (s, 2H), 1.24
(s, 4H). HRMS (APCI) Calcd for C24H34N4O6 498.25; found 521.2368 [M+Na]+
Phenylalanine-methylester-bisurea-hexyl
3L: 1H NMR (400 MHz, DMSO-d6) δ 7.29 (t, J = 7.4 Hz, 5H), 7.22 (t, J = 7.1 Hz, 3H), 7.16 (d, J =
7.3 Hz, 5H), 6.16 – 6.02 (m, 5H), 4.41 (td, J = 8.0, 5.4 Hz, 2H), 3.60 (s, 6H), 2.93 (pt, J = 13.7, 6.7
Hz, 10H), 2.71 – 2.64 (m, 1H), 1.30 (q, J = 6.6 Hz, 5H), 1.21 (dd, J = 7.5, 3.9 Hz, 5H), 1.03 (t, J =
7.2 Hz, 1H). HRMS (APCI) Calcd for C28H38N4O6 526.28; found 549.2684 [M+Na]+
3D: 1H NMR (400 MHz, DMSO-d6) δ 7.33 – 7.17 (m, 6H), 7.22 – 7.12 (m, 4H), 6.15 – 6.01 (m,
4H), 4.40 (td, J = 8.1, 5.6 Hz, 2H), 3.59 (s, 6H), 3.01 – 2.82 (m, 9H), 1.30 (q, J = 6.6 Hz, 5H), 1.24
– 1.14 (m, 6H). HRMS (APCI) Calcd for C28H38N4O6 526.28; found 549.2684 [M+Na]+
3D-L: 1H NMR (400 MHz, DMSO-d6) δ 6.15 – 5.97 (m, 4H), 4.40 (td, J = 8.0, 5.6 Hz, 2H), 3.59
(s, 6H), 3.01 – 2.78 (m, 9H), 2.46 (s, 3H), 2.31 (s, 1H)(toluen), 1.30 (q, J = 6.8 Hz, 5H), 1.25 –
1.15 (m, 5H). HRMS (APCI) Calcd for C28H38N4O6 526.28; found 549.2684 [M+Na]+
12
3.3 Solubility/gelation and gel straight tests
3.3.1 Solubility test
The solubility test were carried out for each of the potential gelators separately. Each
compound was weight on a 4 digit balance, 10 mg ± 0,5 mg (for solubility test accuracy is
not too important since most compounds gel in a relatively vide region and this is mostly to
see in what solvents the compound is soluble in, (too soluble won’t gel and insoluble
definitely will not). The weight material is then placed in vials (remember to mark vials
according to solvent) and 1 mL of the appropriate solvent added. To help with dissolution
the vials are sonicated and then heated (note: to help dissolution further make sure to grind
the material into fine powder in mortal before adding/weighing). After vials have cooled
back to room temperature a light sonication can help to start the gelation process.
3.3.2 Gelation test at higher concentration
Gelation test at higher concentration are carried out in the exactly same way as solubility
test but instead of using 10 mg, 40 mg of gelator was used instead and the error was kept to
about ±0,2 mg.
3.3.3 Tgel test
Tgel test was performed in a sealed vial instead of a test tube to keep the volume of solvent
at a constant. It is also important to keep the error in weight (of compound) between vials
as small as possible preferably 0 or 0,1mg. The same procedure for gel formation as for the
gelation test is followed. The appropriate amount of gelator (determined for each gelator in
the gel-tests) is weight out in the vial, the solvent added and the solution heated and
sonicated. Since gel formation time can differ between gelators and/or solvent each vial
was left out (sealed) for approximately 24 hours before the test took place. A glass ball
(approximately 100 mg in weight) was then carefully placed on top of the gel, the vial
placed in an oil bath at room temperature and the oil slowly heated until the glass ball
comes in contact with the bottom of the vial (when the strength of the gel is not enough to
hold it or the gel has dissolved) at that time accurate temperature is read of the
thermometer in the oil and that head put down as Tgel or gel-sol temperature.
13
4 Results and discussion
4.1 Synthesis
As can be seen in the experimental section, the synthesis can be broken down into two
parts, the synthesis of the amino acid esters (note that only three of the esters were
synthesized and other esters are commercially available and used as purchased) and the
synthesis of the gelators themselves.
4.1.1 Synthesis of amino acid esters
The reaction used for the synthesis of the amino acid ester uses thionyl chloride to form
acid chloride (amino acid chloride), which reacts with alcohol (in this case methanol since
the ester wanted is a methylester) to form the ester. The reaction is relatively simple as can
be seen in the experimental section and the mechanism is shown in figure 4.1.
Figure 4.1: Mechanism of esterification using thionyl chloride, using phenylalanine as an example.
14
4.1.2 Synthesis of gelators.
The reaction used for the synthesis of the gelators is a simple nucleophilic reaction. The
free electron pair on the nitrogen atom in the amino acid “attacks” the carbon in the
isocyanato group of the alkyl chain. This results in both nitrogen atoms being charged but
that is fixed by proton transfer from one nitrogen to the other, as can be seen in figure 4.2.
The reaction is performed for both sides of the 1,6- diisocyanatohexane. The simplicity of
the mechanism for this reaction makes all amino acids interchangeable. Which means that
one simple reaction can be used to make a series of amino acid based urea gelators. All that
is required is a compound containing isocyanate and any amino acid or amino acid ester.
Figure 4.2: Mechanism of synthesis for gelator molecules, using phenylalanine methyl ester as an example.
4.2 Gelation tests
As stated before the gelation test were divided into two parts. The first one was performed
at 1 wt% to find out in which solvents a given potential gelator is soluble as well as to see
if it would gel at 1 wt% or to get an indication that it would gel at a higher concentration.
The second part is to check the gelation properties in detail for the potential gelator
obtained in the initial screening (part one) at a higher concentration.
15
4.2.1: Gelation test with various solvents at 1 wt%
Table 4.1: Solvent tests for amino acid based urea gelators, at 1 wt%/V. Due to lack of chemical 1D-L and
3D-L where not tested, since solubility should theoretically very similar to the other enantiomers. See solvent
table for solvent related to each solvent number, table 6,1.
Solvent number 1L 1D 1D-L 2L 2D 2D-L 3L 3D 3D-L 1 I I I I I I I 2 I I I I I I I 3 P P PS PS PS P P 4 I I I PS I I I 5 I CO+Cl P PS P CO CO 6 P S Cl S P CO CO 7 PG CO P PS P G G P 8 P CO Cl + MP PG P CO CO 9 I S P CO I G/PG G G 10 P S CL+ MP P P S CO 11 P CO+Cl P P P G G G 12 I CO P P P PG/G PG G 13 I I I I I I I 14 I P P P P P PG P 15 P/CO CO P P P S S 16 P/CO P P P P PG/G G G 17 P S MP CO P S S S 18 P S MP CO P S S 19 P CO P CO P CO CO 20 P/CO Cl P CO P G G G 21 P S MP CO P S S 22 P S MP+Cl CO P S S 23 S Cl P CO CO G G G 24 CO S P CO P P CO 25 CO CO P P P G PG G 26 P CO P P P G G G 27 CO CO CO PG CO G G G 28 P S Cl CO P S S 29 CO CO P CO P CO PG G 30 S S CO PG S G G G 31 I P I I I I I I = insoluble, PS = partially soluble / slight precipitation S= soluble/solution P = precipitate, MP
= micelle like precipitate, Cl = crystalline, CO = coagulant PG = partial gel, G = gel
16
As can be seen in Table 4.1, there are some irregularities in solubility and gelation between
some of the enantiomers. The solubility of 1L is different from 1D and on top of that it
made a partial gel in a solvent (THF) 1D didn’t. Similar observations were found for 2D
but on a larger scale. 2D made partial gels in three solvents (methanol, o-xylene and
nitrobenzene) the other enantiomers didn’t. If the NMR’s for 1L and 1D are compared
there are two duplicate peaks for 1L, the peaks for the urea show up twice and each
integrates to less than two but are close to that when added. The most likely explanation
for the differences in both NMR and solubility/gelation is that some part of 1L is in the
acid form instead of the ester form. This is further supported by the fact that during
distilling of chloroform a distinctly acidic smell was identified once and when tested with
litmus the pH was 1. And the same is thought to be true for 2D (is partially in the acid
form). In comparison to the other two (1 and 2 all enantiomers) 3 did a lot better as a
gelator. 3L and 3D gelled in THF (3D-L did not), D and D-L gelled in Mesitylene and D
also made a partial gel in acetonitrile. On top of that all three enantiomers (L, D and D-L)
gelled in ethyl acetate, benzene, 2-butanole, isopropanol, toluene, p, m and o-xylene and
nitrobenzene.
Figure 4.3: Gels of 3L in toluene and ethyl acetate.
17
4.2.2 Gel tests at a higher concentration
For the second test a concentration of 4 wt% was chosen, this was done because it was
high enough that if the compound was a gelator it would most likely show at least some gel
like behaviour and if the solution would be over saturated it would be simple to bring it
down to 2 wt% by simply adding an additional ml of the appropriate solvent. For this
experiment it was decided to only use enantiomers of 1 and 2 since 3 gels well in a verity
of solvents at 1 wt%. The solvents were also cut down and only solvents that showed
promise in the earlier test carried on.
Table 4.2: Gel test for all enantiomers of 1 in different solvents.
Here we can see the gel test for the enantiomers of 1. All three enantiomers make
hydrogels at 4 wt% in a 50/50 (V/V) mixture of both methanol/water and ethanol/water. As
stated earlier it is uncommon that gelators form both hydrogels and organogels, and that
holds for this gelator. The reason 1D-L was only tested as a hydrogel is that most of the
compound was lost during the purification process, when the acid form of the compound
was removed from the ester (as mention before the chloroform became acidic and some of
the reactions were partially converted to the acid form). It is also noteworthy that the batch
of 1L that made hydrogel was not from the same synthesis as the one used for solvents 7-
25 or in the solubility test (a NMR of it is available in supplementary information as 1L-b,
along with the one used for solubility test 1L).
As can be seen from table 4.3 the consistency among enantiomers of 2 is not much at all.
2D-L only made one partial gel (in nitrobenzene) and 2L made one partial gel (in ethanol)
and one gel (in o-xylene) while 2D gelled in all of the selected solvents. As mentioned
Solvent 1L 1D 1D-L
7 I CO
8 I S
10 I S
25 PS P
8/31 V=50/50 G G G
10/31 V=50/50 G G G
18
before it is believed that 2D is partially in the acid form and that might be the explanation
for why it gels better. It might be that the acid form is simply a better gelator, it might also
be the interaction between the acid and ester forms, but to confirm that further experiments
on the phenylalanine-bisurea-hexyl would have to be performed.
Table 4.3: Gel test for all enantiomers of 2 in different solvents.
Solvent 2L 2D 2D-L
10 PG G P
16 P G P
23 P G P
27 G G P
30 S G PG
Figure 4.4: Gels of 2D in o-xylene, nitrobenzene and ethanol
4.3 Tgel test.
An excellent property of gel is that the gel strength can be found from the gel to solution
transition temperature test (Tgel), where a small ball (around 100 mg in weight, often made
of glass) is carefully placed on top of a gel (that has been formed in a sealed vial in effort
to keep the volume of solvent constant, forgo evaporation) which is then placed in a heat
19
bath (usually some kind of oil or other liquid with a high boiling point and low toxicity)
and the temperature is slowly raised until the ball falls down to the bottom of the vial. The
temperature of the heat bath (and thus the former gel/ solution) is then marked as Tgel. For
the Tgel test a few gels were selected for the testing of gel-sol temperature. None of the
hydrogels were used (enantiomers of 1 were not tested) but all gels of 2 were tested. For
enantiomers of 3 two solvents were selected no. 9 and 20 (ethyl acetate and toluene) for all
the enantiomers as well as a conglomerate mixture (50/50 by weight) of D and L, which
will be represented as 3D+L.
Table 4.4: Tgel test for all enantiomers of 2 that gelled. Average temperature shown below each row of
results of test for given compound and solvent.
2L Solvent exact mass (mg) T °C 1 27 39,9 119,8 2 27 40 106,2 3 27 40,1 106,3
2D Average Temperature 106,25 1 10 40,1 39,0 2 10 39,9 42,3 3 10 40,1
2D Average Temperature 40,7 1 16 40,0 68,0 2 16 39,9 66,0 3 16 40,0 65,9
2D Average Temperature 66,6 1 23 39,9 80,0 2 23 40,0 82,8 3 23 40,1 81,2
2D Average Temperature 81,3 1 27 40,1 77,5 2 27 40,1 76,2 3 27 40,1 75,0
2D Average Temperature 76,2 1 30 40,0 >180 2 30 40,0 >180 3 30 39,9 >180
Average Temperature >180
As can be seen in previous tables (Table 4.3 and 4.4) 2L only made gel in one solvent (o-
xylene) the average gel-sol temperature measured for it was put at 106,25 °C since the first
measurement was significantly higher than the other two. 106,25 °C is still quite a bit
20
higher than the gel-sol temperature for its D enantiomer, and for that there are two possible
reasons.
Table 4.5: Tgel test for all enantiomers as well as conglomerate mixture (50/50 by weight) of D and L for 3 in
ethyl acetate and toluene. Average temperature shown below each row of results of test for given compound
and solvent.
3L Solvent exact mass (mg) T °C
1 9 10,0 62,2
2 9 10,0 61,8
3 9 10,0 59,8
Average Temperature 61,3
1 20 10,0 84,5
2 20 10,0 86
3 20 9,9 84,2
Average Temperature 84,9
3D
1 9 10,1
2 9 10,0 54,5
3 9 10,0 55,2
Average Temperature 54,9
1 20 10,1 91,2
2 20 10,0 90,5
3 20 9,9 90,8
Average Temperature 90,8
3D-L
1 9 10,1 54,0
2 9 10,1 54,8
3 9 10,1 54,2
Average Temperature 54,3
1 20 10,0 86
2 20 9,9 86,8
3 20 10,1 86,5
Average Temperature 86,4
3D+L
1 9 L- 4,9 + D- 5,1 75,00
2 9 L- 5,0 + D- 5,0 73
3 9 L- 5,1 + D- 5,0 72,2
Average Temperature 73,40
1 20 L- 4,9 + D- 5,1 96,2
2 20 L- 5,0 + D- 5,0 98,8
3 20 L- 4,9 + D- 5,0 95,8
Average Temperature 96,9
The first one is as has been stated before, it is believed that the D enantiomer is partially in
the acid form. Though it makes gel in more solvents it might weaken the strength of the gel
in solvents that the pure ester would form. The second one is error in measurements. Since
21
a clear glass ball was used, in an opaque white gel of 2L that results in a difficulty to assess
the accurate position of the ball and therefore the exact temperature it comes in contact
with the bottom of the vial was difficult to evaluate. After that a blue ball of the same mass
was used instead. For 2D there is an interesting trend that can be seen between the gel-sol
temperature (Tgel) and the boiling point of the solvent used. The higher the boiling point of
the solvent the higher the gel-sol temperature, with one exception. Even though the boiling
point of o-xylene is 12 °C higher than for chlorobenzene the average gel-sol temperature is
5,1 °C lower. This also happens to be around 30 °C lower than for 2L in the same solvent.
It is not clear why this anomalous behaviour occurs and would need further studies to
explain this, which is ongoing. As can clearly be seen from table 4.5 there is a distinct
difference in gel-sol temperature between the 3 enantiomers and the conglomerate mixture.
Out of the three compounds (excluding the conglomerate mixture) 3L has the highest Tgel
in ethyl acetate. Tgel for 3D and 3D-L are in principle the same when standard deviation
and error are taken into consideration.
On the other hand, 3D has the highest (among these three) Tgel in toluene, whereas,
the other two are quite similar (the difference is still a bit higher from the previous example
but might again be explained by the similar things) The most interesting part of the result is
the fact that the Tgel for the conglomerate mixture is significantly higher in all cases
compared to the individual enantiomers (3L and 3D) as well as the racemic (D-L) mixture
of the compound. For the ethyl acetate gel the average Tgel is 12,1 °C higher than for the
highest of the other three (3L) and for the toluene gel it is 6,1 °C higher than the highest of
the others (3D). The reasons for this are not as yet clear, since theoretically the
conglomerate mixture should have almost identical properties as the racemic mixture.
22
5 Conclusion
The specific aim of the project was to develop new amino acid based urea gelators
(supramolecular gelators) as well as to further investigate the properties of one that had
been developed by the project manager. Furthermore, these type of gelators can have
potential applications ranging from controlling crystal growth to drug delivery systems.
Therefore developing new gelators is highly desirable and could have a great impact in the
development of this relatively new field of supramolecular chemistry in Iceland. In the last
decades, interest in supramolecular gels has increase immensely and understanding of
supramolecular chemistry of gel formation is still developing. Designing a gelator is a
tough task, since there are countless factors that can affect the formation of the gel, and
theoretically prediction of gel formation often fails. One of the best method is to correlate
the crystal structure with the structure of the gel fibrils. To form the gel network, it is
important to incorporate certain functional groups that can form non-covalent interactions
with the right orientation and form the 3-D fibril network that traps the solvent.
The syntheses of all three chemicals (9 if all enantiomers are counted) were carried out
successfully without any major problems. For a few reactions, contaminated chloroform
(turned acidic most likely from interaction with P2O5, which turns to phosphoric acid when
reacted with water) converted a portion of some products to the acid form of the amino
acid. However, mostly these compounds were purified so only the ester form remained.
Furthermore, it was proven that in the right solvent or solvent blend all three compounds
would gel. Valinemethylester-bisurea-hexyl (1) proved to be a hydrogel, gelating in a
50/50 (V/V) mixture of both methanol/water and ethanol/water at 4% by weight for all
enantiomers. Phenylglycinemethylester-bisurea-hexyl (2) turned out to gel in o-xylene but
only for L and D (not the racemic mixture D-L). The D enantiomer of 2 gelled in the most
solvents out of all enantiomers of 2, the hypothesis is that this is probably due to the high
concentration of Phenylglycine-bisurea-hexyl (acid form) in the compound, which means
that the acid form might be a better gelator than the ester and studies are ongoing.
Phenylalaninemethylester-bisurea-hexyl (hypothesis) was as expected a great gelator,
gelling in 13 solvents and usually both enantiomers as well as the racemic mixture. The
Tgel tests showed that the gel-sol temperature generally follows a similar trend as the
boiling point of the solvent, the higher the boiling point the higher the Tgel. Interestingly
23
the Tgel for the conglomerate mix of D and L proved to be significantly higher than that of
D, L or D-L. The reason for this is still unknown but one can speculate that this arise from
the individual interactions of D and L and the formation of stronger non-covalent bond
then when the compound is uniform.
Although this project exceeded its time limits by a great deal the results cannot be argued
with. This project accomplishes the discovery and synthesis of two supramolecular
gelators, as well as pointing out a new phenomenon when it comes to the strength of
conglomerate supramolecular gels.
25
Solvent number Solvent Bp (°C)
1 Diethyleter 35
2 Pentane 36
3 DCM 40
4 Tert butyl metyl ether 55
5 Acetone 56
6 Chloriform 61
7 THF 65
8 Methanol 65
9 Ethyl acetate 77
10 Ethanol 79
11 Benzene 80
12 2-Butanone 80
13 Cyclohexane 81
14 Acetonitrile 82
15 Isopropanol 83
16 1,2-dichloroethane 84
17 n-propanol 97
18 2-Butanol 100
19 Dioxane 101
20 Toluen 111
21 n-Butanol 118
22 2-Pentanol 119
23 Chlorobenzene 132
24 n-Pentanol 137
25 p-Xylene 138
26 m-Xylene 139
27 o-Xylene 144
28 Cyclohexanone 156
29 Mesitylene 165
30 Nitrobenzene 210
31 Water 100
6 Supplementary information
6.1 Solvent Table
26
6.2 Nuclear Magnetic Resonance Spectroscopy
6.2.a General
The 1H–NMR spectra were recorded on a Bruker Advance 400 NMR spectrometer using
CDCl3 (s, 7.26 ppm) or DMSO (qu, 2,51 ppm) as the NMR solvent (1H–NMR: 400 MHz).
6.2.x Spectral data
6.2.1: 1H-NMR of D-L-phenylalanine-methylester
Figure 6.1: 1H–NMR of A1 (D-L-phenylalanine-methylester)
27
6.2.2: 1H-NMR of L-phenylalanine-methylester
Figure 6.2: 1H–NMR of A2 (L-phenylalanine-metylester)
6.2.3: 1H-NMR of D-L-phenylglycine-methylester
Figure 6.3: 1H–NMR of A3 (D-L-phenylglycine-methylester)
28
6.2.4: 1H-NMR of L-valine-methylester-bisurea-hexyl
Figure 6.4: 1H–NMR of 1L
6.2.5: 1H-NMR of L-valine-methylester-bisurea-hexyl-b
Figure 6.5: 1H–NMR of 1Lb
29
6.2.6: 1H-NMR of D-valine-methylester-bisurea-hexyl
Figure 6.6: 1H–NMR of 1D
6.2.7: 1H-NMR of D-L-valine-methylester-bisurea-hexyl
Figure 6.7: 1H–NMR of 1D-L
30
6.2.8: 1H-NMR of L-phenylglycine-methylester-bisurea-hexyl
Figure 6.8: 1H–NMR of 2L
6.2.9: 1H-NMR of D-phenylglycine-methylester-bisurea-hexyl
Figure 6.9: 1H–NMR of 2D
31
6.2.10: 1H-NMR of D-L-phenylglycine-methylester-bisurea-hexyl
Figure 6.10: 1H–NMR of 2D-L
6.2.11: 1H-NMR of L-phenylalanine-methylester-bisurea-hexyl
Figure 6.11: 1H–NMR of 3L
32
6.2.12: 1H-NMR of D-phenylalanine-methylester-bisurea-hexyl
Figure 6.12: 1H–NMR of 3D
6.2.13: 1H-NMR of D-L-phenylalanine-methylester-bisurea-hexyl
Figure 6.13: 1H–NMR of 3D-L
33
6.3 Mass Spectroscopy
6.3.1: Mass for L-valine-methylester-bisurea-hexyl
Figure 6.14 : Mass for 6.3.1: Mass for L-valine-methylester-bisurea-hexyl
6.3.2: Mass for D-valine-methylester-bisurea-hexyl
Figure 6.15 : Mass for 6.3.1: Mass for D-valine-methylester-bisurea-hexyl
34
6.3.3: Mass for D-L-valine-methylester-bisurea-hexyl
Figure 6.15 : Mass for 6.3.1: Mass for D-L-valine-methylester-bisurea-hexyl
6.3.4: Mass for L-phenylglycine-methylester-bisurea-hexyl
Figure 6.16 : Mass for 6.3.1: Mass for L-phenylglycine-methylester-bisurea-hexyl
35
6.3.5: Mass for D-phenylglycine-methylester-bisurea-hexyl
Figure 6.17 : Mass for 6.3.1: Mass for D-phenylglycine-methylester-bisurea-hexyl
6.3.6: Mass for D-L-phenylglycine-methylester-bisurea-hexyl
Figure 6.18 : Mass for 6.3.1: Mass for D-L-phenylglycine-methylester-bisurea-hexyl
36
6.3.7: Mass for L-phenylalanine-methylester-bisurea-hexyl
Figure 6.19 : Mass for 6.3.1: Mass for L-phenylalanine-methylester-bisurea-hexyl
6.3.8: Mass for D-phenylalanine-methylester-bisurea-hexyl
Figure 6.20 : Mass for 6.3.1: Mass for D-phenylalanine-methylester-bisurea-hexyl
37
6.3.9: Mass for D-L-phenylalanine-methylester-bisurea-hexyl
Figure 6.21 : Mass for 6.3.1: Mass for D-L-phenylalanine-methylester-bisurea-hexyl
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